Sildenafil inhibits β-adrenergic-stimulated cardiac contractility in humans
Sildenafil inhibits β-adrenergic-stimulated cardiac contractility in humans
复制标题
DOI：
10.1161/circulationaha.105.540500
复制
发表时间：
2005-10-25
期刊：
影响因子：
37.8
通讯作者：
Kass, DA
中科院分区：
文献类型：
--
作者：
Borlaug, BA;Melenovsky, V;Kass, DA
背景-西地那非抑制磷酸二酯酶5（PDE 5A），以提高细胞内环鸟苷酸并诱导血管舒张。这种效果导致其用于治疗勃起功能障碍。虽然其对静息心脏功能的影响似乎很小，但最近的动物研究表明，西地那非对β-肾上腺素能或压力超负荷刺激的心脏可能具有强效作用。因此，我们测试是否西地那非钝多巴酚丁胺刺激的心脏功能在human.Methods和结果35名健康志愿者进行了随机，双盲，安慰剂对照研究中，心脏功能进行了评估，多巴酚丁胺之前和之后口服西地那非（100毫克，n =19）或安慰剂（n = 16）。超声多普勒和无创血压数据产生负荷无关的收缩指数（最大功率指数和收缩末期弹性），射血分数和舒张功能的措施。在最初的多巴酚丁胺试验中，两个治疗组的收缩和舒张功能改善相似（例如，安慰剂组峰值功率指数上升80 +/- 28%，西地那非组上升82 +/- 31%; P = NS）。然而，在随后接受西地那非治疗的受试者中，他们的第二次多巴酚丁胺反应明显减弱，峰值功率、射血分数和收缩末期弹性变化分别降低了32 +/-34%、66 +/-64%和56 +/-63%（与初始反应相比，P < 0.001）。这与安慰剂组形成对比，安慰剂组在两次多巴酚丁胺试验中显示出相似的功能反应。西地那非治疗并没有显着改变多巴酚丁胺诱导的舒张期变化与placebo. Conclusions结果相比，PDE 5A抑制西地那非钝收缩反应β-肾上腺素能刺激。这一发现支持PDE 5A在人类心脏中的活性及其在改变刺激的心脏功能中的作用。
Background-Sildenafil inhibits phosphodiesterase 5 (PDE5A) to elevate intracellular cGMP and to induce vasodilation. This effect has led to its use for treating erectile dysfunction. Although its influence on rest heart function has appeared minimal, recent animal studies suggest that sildenafil can have potent effects on hearts stimulated by beta-adrenergic or pressure overloads. We therefore tested whether sildenafil blunts dobutamine-stimulated cardiac function in humans.Methods and Results-Thirty-five healthy volunteers underwent a randomized, double-blind, placebo-controlled study in which cardiac function was assessed in response to dobutamine before and after oral sildenafil (100 mg, n =19) or placebo ( n = 16). Echo Doppler and noninvasive blood pressure data yielded load-independent contractility indexes ( maximal power index and end-systolic elastance), ejection fraction, and measures of diastolic function. In the initial dobutamine test, systolic and diastolic function improved similarly in both treatment groups (eg, peak power index rose 80 +/- 28% in the placebo group and 82 +/- 31% in the sildenafil group; P = NS). However, in subjects who then received sildenafil, their second dobutamine response was significantly blunted, with peak power, ejection fraction, and end-systolic elastance changes reduced by 32 +/- 34%, 66 +/- 64%, and 56 +/- 63%, respectively ( each P < 0.001 versus the initial response). This contrasted to the placebo group, which displayed similar functional responses with both dobutamine tests. Sildenafil treatment did not significantly alter diastolic changes induced by dobutamine compared with results with placebo.Conclusions-PDE5A inhibition by sildenafil blunts systolic responses to beta-adrenergic stimulation. This finding supports activity of PDE5A in the human heart and its role in modifying stimulated cardiac function.